Pharmaceutical, biological, biochemical and biotech processes are performed in increasing measure by means of so called single-use, process solutions, e.g. process plants applying single-use technology. Such process plants comprise pipelines or reactors, which are embodied as single-use containers. These are also referred to as disposables, respectively disposable bioreactors or single-use bioreactors, respectively single-use components. These single-use containers can be flexible containers, for example, bags, hoses or fermenters. Bioreactors or fermenters frequently have supply and drain lines, which can be embodied, for example, as hoses. There can be rigid tubular pieces inserted in the supply and drain lines. After termination of a process, the single-use container can be disposed of. In this way, complex cleaning and sterilization methods are avoided. Generally, the use of single-use containers avoids the risk of cross contamination and therewith increases process safety.
In order to monitor or control the processes, it can be necessary to measure physical or chemical, measured variables of the media contained in the single use, process containers. Examples of sensors used in such cases include optical, however, also electrochemical, potentiometric or amperometric sensors or conductivity sensors. Proved advantageous are so-called multi-sensors, which are embodied to measure a plurality of mutually differing, measured variables. Such multi-sensors have, frequently, a number of measuring transducers, wherein each measuring transducer is embodied for registering measured values of one of the measured variables to be monitored.
The processes performed in single-use containers run in a closed system, i.e., without connection to the environment outside of the single-use container. Since sterile conditions are frequently required, the single-use container must be sterilized before introduction of the process media. Gamma radiation is frequently used for this purpose in biochemical, biological, biotechnological and pharmaceutical applications. Also, while the processes are running in a single-use fermenter or single-use reactor, the penetration of impurities, such as germs, from the environment into the interior of the single-use container must be prevented, in order not to degrade or corrupt the process. The same holds also for supply and drain lines communicating with the single-use fermenter or single-use reactor.
One or a number of sensors integrated in the single-use container can be sterilized together with the single-use container. As a result of the sterilizing and/or for the case in which a longer time span lies between the sterilizing and the start-up of the single-use container and the integrated sensors, properties of the integrated sensors can change, which can lead to a change of the respective sensor characteristic lines, e.g., to a zero point drift. Potentiometric and amperometric sensors frequently include membranes, which ideally should be stored moist. Moist storage assures that the sensors output reliable measured values immediately from start-up.
Another complication is the fact that sterilizing by means of gamma radiation required for many biochemical and biotech processes can lead to the destruction of electronic components of the sensors. It has therefore been provided, for example, in DE 10 2011 080 956 A1, to embody sensors, which are integrated into the wall of single-use containers to be sterilized, as analog, single use sensors and to connect them, only after sterilizing, releasably with an electronics unit arranged outside of the single-use container and comprising sterilizable components. The electronics unit is embodied to process the analog measured values provided by the sensor further. The electronics unit can, after terminating the process, be used again and be connected with a new, sterilized, single use sensor in another process installation. Since the complete measuring path, which includes the analog sensor and the electronics unit, is present only upon start-up, it would likewise be desirable in such cases to provide, directly before start-up, an efficient calibration, verification or even adjusting of the sensors integrated in the single-use container.
Known from EP 2734611 B1 is a sensor arrangement, which is securable on a process container, and which includes a housing, in which a probe tube can be moved axially into and out of the process container. Accommodated in the probe tube is a sensor, e.g., a pH sensor, whose end section, which must be brought in contact with a measured medium for registering measured values of a measured variable, can protrude out of the probe tube. Connected with the probe tube via an axially extending strut is a disc shaped closure element. In a first position of the probe tub moved into the housing, the closure element closes the housing at the process container end and the sensor element of the sensor is arranged in a chamber formed within the housing. Contained in this chamber can be a liquid, for example, a calibration liquid. In a second position of the probe tube moved out of the housing, the closure element is arranged spaced out of the housing, so that the chamber formed within the housing is open to the process container, and the sensor can contact a medium contained in the process container for performing measurements. Since the closure element is arranged spaced from the sensor element in the axial direction toward the process container, the probe tube must be moved a relatively great distance into the process container, in order to bring the sensor into contact with a measured medium contained in the process container. Additionally, in the case of this known sensor arrangement, a movement of liquid from the chamber formed within the housing into the process container, respectively a movement of a medium from the process container into the chamber, cannot be excluded.
Described in EP 2363704 B1 is a sensor arrangement with a sensor system to be calibrated and a compartment containing a calibration means, wherein the sensor system and the compartment are accommodated in a housing movably relative to one another. The housing is connectable with a process container. The sensor system can be calibrated in the compartment and then by an irreversibly executable, relative movement between the sensor system and the compartment be brought into a measurement ready position. The apparatus is relatively complicated in construction. For preventing movement of liquid from the chamber formed within the housing into the process container, a septum is provided, through which a sensitive element of the sensor can be moved. Since the movement of the sensor is irreversible, the sensor can no longer be moved back. Therewith, indeed, a movement of process media from the process container into the compartment is suppressed. On the other hand, therewith, a renewed calibration or regeneration of the sensor system in the compartment after a certain period of use is excluded.